tbuckley/cabot-search huggingface dataset:
Monitoring tumour resistance to the BRAF inhibitor combination regimen in colorectal cancer patients via circulating tumour DNA
Authors: Liu-Fang Ye, Zi-Yao Huang, Xiao-Xi Chen, Zhi-Gang Chen, Si-Xian Wu, Chao Ren, Ming-Tao Hu, Hua Bao, Ying Jin, Feng Wang, Feng-Hua Wang, Zi-Ming Du, Xue Wu, Huai-Qiang Ju, Yang Shao, Yu-Hong Li, Rui-Hua Xu, De-Shen Wang
Journal: Drug Resistance Updates (2022)

This study aimed to identify mechanisms of drug resistance to the combination of vemurafenib, irinotecan, and cetuximab (VIC) in BRAFV600E metastatic colorectal cancer (mCRC).Forty-one patients with BRAFV600E mCRC from July 2018 and June 2020 were evaluated, with tissue and/or plasma samples collected. We profiled tissue and plasma samples using whole-exome sequencing and targeted sequencing of 425 cancer-relevant genes. Clinical cohort analysis from published studies was performed to consolidate our findings.BRAF mutant in baseline plasma and its dynamics are significantly associated with VIC-related response, and concurrent RNF43 mutation significantly sensitises tumour to VIC treatment. VIC resistance frequently involves genes in PI3K, MAPK pathway, and several novel resistance mechanisms such as TGFBR2 and SMAD4 mutations, and copy-number gains in PTK2, MYC, and GATA6 have been identified. We also firstly describe acquired altered genes in DNA damaging repair pathway, occurring in 33 % of patients after VIC treatment, and particularly, patients with this pre-treatment resistance subclones developed inferior responses, along with higher tumour mutation burden both at baseline and progression plasma.Analysis of ctDNA can provide novel insights into molecular resistance mechanisms to VIC in BRAFV600E mCRC patients, allowing accurate guidance for clinicians in personalised treatment strategies.
Correction to: Mitochondrial H2S Regulates BCAA Catabolism in Heart Failure
Journal: Circulation Research (2022)

a correction was needed.In Figure 3B, which illustrates the LV ejection fraction throughout the 12-week study for 3-MST KO and wild-type control mice, the bar graph was misplaced.During figure processing, the bar graph prepared for the Figure 6E was inadvertently put in Figure 3B.The results section and discussion are correct in their original form.This correction does not change the outcomes or interpretation of the observations made in the manuscript.
Enhancing therapeutic anti-cancer responses by combining immune checkpoint and tyrosine kinase inhibition
Authors: Roger J. Daly, Andrew M. Scott, Oliver Klein, Matthias Ernst
Journal: Molecular Cancer (2022)

Abstract Over the past decade, immune checkpoint inhibitor (ICI) therapy has been established as the standard of care for many types of cancer, but the strategies employed have continued to evolve. Recently, much clinical focus has been on combining targeted therapies with ICI for the purpose of manipulating the immune setpoint. The latter concept describes the equilibrium between factors that promote and those that suppress anti-cancer immunity. Besides tumor mutational load and other cancer cell-intrinsic determinants, the immune setpoint is also governed by the cells of the tumor microenvironment and how they are coerced by cancer cells to support the survival and growth of the tumor. These regulatory mechanisms provide therapeutic opportunities to intervene and reduce immune suppression via application of small molecule inhibitors and antibody-based therapies against (receptor) tyrosine kinases and thereby improve the response to ICIs. This article reviews how tyrosine kinase signaling in the tumor microenvironment can promote immune suppression and highlights how therapeutic strategies directed against specific tyrosine kinases can be used to lower the immune setpoint and elicit more effective anti-tumor immunity.
Retraction Note to: Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway
Authors: Mingjun Yu, Yixue Xue, Jian Zheng, Xiaobai Liu, Hai Yu, Libo Liu, Zhen Li, Yunhui Liu
Journal: Molecular Cancer (2022)
Ensuring Assisted Living Provides the Assistance Residents Need
Authors: Kenneth Lam, Kenneth E. Covinsky
Journal: JAMA Network Open (2022)

Sheryl Zimmerman, PhD; Philip D. Sloane, MD, MPH; Christopher J. Wretman, PhD; Kevin Cao, BS; Johanna Silbersack, MSW; Paula Carder, PhD; Kali S. Thomas, PhD; Josh Allen, RN; Kim Butrum, RN, MS; Tony Chicotel, JD, MPP; Pat Giorgio, MPS; Mauro Hernandez, PhD; Helen Kales, MD; Paul Katz, MD; Juliet Holt Klinger, MA; Margo Kunze, RN; Christopher Laxton, CAE; Vicki McNealley, PhD, MN, RN; Suzanne Meeks, PhD; Kevin O'Neil, MD; Douglas Pace, NHA; Barbara Resnick, PhD, RN; Lindsay Schwartz, PhD; Dallas Seitz, MD, PhD; Lori Smetanka, JD; Kimberly Van Haitsma, PhD
Glycemic Control Trajectories and Risk of Perinatal Complications Among Individuals With Gestational Diabetes
Authors: Rana F. Chehab, Assiamira Ferrara, Mara B. Greenberg, Amanda L. Ngo, Juanran Feng, Yeyi Zhu
Journal: JAMA Network Open (2022)

Glycemic control is the cornerstone of gestational diabetes management. Glycemic control trajectories account for differences in longitudinal patterns throughout pregnancy; however, studies on glycemic control trajectories are scarce.
Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 in osteoarthritis
Authors: Alexander J Knights, Easton C Farrell, Olivia M Ellis, Lindsey Lammlin, Lucas M Junginger, Phillip M Rzeczycki, Rachel F Bergman, Rida Pervez, Monique Cruz, Eleanor Knight, Dennis Farmer, Alexa A Samani, Chia-Lung Wu, Kurt D Hankenson, Tristan Maerz
Journal: Annals of the Rheumatic Diseases (2022)

Synovium is acutely affected following joint trauma and contributes to post-traumatic osteoarthritis (PTOA) progression. Little is known about discrete cell types and molecular mechanisms in PTOA synovium. We aimed to describe synovial cell populations and their dynamics in PTOA, with a focus on fibroblasts. We also sought to define mechanisms of synovial Wnt/β-catenin signalling, given its emerging importance in arthritis.We subjected mice to non-invasive anterior cruciate ligament rupture as a model of human joint injury. We performed single-cell RNA-sequencing to assess synovial cell populations, subjected Wnt-GFP reporter mice to joint injury to study Wnt-active cells, and performed intra-articular injections of the Wnt agonist R-spondin 2 (Rspo2) to assess whether gain of function induced pathologies characteristic of PTOA. Lastly, we used cultured fibroblasts, macrophages and chondrocytes to study how Rspo2 orchestrates crosstalk between joint cell types.We uncovered seven distinct functional subsets of synovial fibroblasts in healthy and injured synovium, and defined their temporal dynamics in early and established PTOA. Wnt/β-catenin signalling was overactive in PTOA synovium, and Rspo2 was strongly induced after injury and secreted exclusively by Prg4hi lining fibroblasts. Trajectory analyses predicted that Prg4hi lining fibroblasts arise from a pool of Dpp4+ mesenchymal progenitors in synovium, with SOX5 identified as a potential regulator of this emergence. We also showed that Rspo2 orchestrated pathological crosstalk between synovial fibroblasts, macrophages and chondrocytes.Synovial fibroblasts assume distinct functional identities during PTOA in mice, and Prg4hi lining fibroblasts secrete Rspo2 that may drive pathological joint crosstalk after injury.
A Clinical Calculator in the Era of Nonoperative Management for Rectal Cancer—How Should We Intensify or Deescalate Surveillance?
Authors: Tsuyoshi Konishi
Journal: JAMA Network Open (2022)

Martin R. Weiser, MD; Joanne F. Chou, MPH; Jin K. Kim, MD; Maria Widmar, MD, MPH; Iris H. Wei, MD; Emmanouil P. Pappou, MD, PhD; J. Joshua Smith, MD, PhD; Garrett M. Nash, MD, MPH; Philip B. Paty, MD; Andrea Cercek, MD; Leonard B. Saltz, MD; Paul B. Romesser, MD; Christopher H. Crane, MD; Julio Garcia-Aguilar, MD, PhD; Deborah Schrag, MD, MPH; Mithat Gönen, PhD
Association of Oncologist Participation in Medicare’s Oncology Care Model With Patient Receipt of Novel Cancer Therapies
Authors: Christopher R. Manz, Angela C. Tramontano, Hajime Uno, Ravi B. Parikh, Justin E. Bekelman, Deborah Schrag
Journal: JAMA Network Open (2022)

Importance Medicare’s Oncology Care Model (OCM) was an alternative payment model that tied performance-based payments to cost and quality goals for participating oncology practices. A major concern about the OCM regarded inclusion of high-cost cancer therapies, which could potentially disincentivize oncologists from prescribing novel therapies. Objective To examine whether oncologist participation in the OCM changed the likelihood that patients received novel therapies vs alternative treatments. Design, Setting, and Participants This cohort study of Surveillance, Epidemiology, and End Results (SEER) Program data and Medicare claims compared patient receipt of novel therapies for patients treated by oncologists participating vs not participating in the OCM in the period before (January 2015-June 2016) and after (July 2016-December 2018) OCM initiation. Participants included Medicare fee-for-service beneficiaries in SEER registries who were eligible to receive 1 of 10 novel cancer therapies that received US Food and Drug Administration approval in the 18 months before implementation of the OCM. The study excluded the Hawaii registry because complete data were not available at the time of the data request. Patients in the OCM vs non-OCM groups were matched on novel therapy cohort, outcome time period, and oncologist specialist status. Analysis was conducted between July 2021 and April 2022. Exposures Oncologist participation in the OCM. Main Outcomes and Measures Preplanned analyses evaluated patient receipt of 1 of 10 novel therapies vs alternative therapies specific to the patient’s cancer for the overall study sample and for racial subgroups. Results The study included 2839 matched patients (760 in the OCM group and 2079 in the non-OCM group; median [IQR] age, 72.7 [68.3-77.6] years; 1591 women [56.0%]). Among patients in the non-OCM group, 33.2% received novel therapies before and 40.1% received novel therapies after the start of the OCM vs 39.9% and 50.3% of patients in the OCM group (adjusted difference-in-differences, 3.5 percentage points; 95% CI, −3.7 to 10.7 percentage points; P = .34). In subgroup analyses, second-line immunotherapy use in lung cancer was greater among patients in the OCM group vs non-OCM group (adjusted difference-in-differences, 17.4 percentage points; 95% CI, 4.8-30.0 percentage points; P = .007), but no differences were seen in other subgroups. Over the entire study period, patients with oncologists participating in the OCM were more likely to receive novel therapies than those with oncologists who were not participating (odds ratio, 1.47; 95% CI, 1.09-1.97; P = .01). Conclusions and Relevance This study found that participation in the OCM was not associated with oncologists’ prescribing novel therapies to Medicare beneficiaries with cancer. These findings suggest that OCM financial incentives did not decrease patient access to novel therapies.
Economic Analysis of Infectious Disease Consultation for<i>Staphylococcus aureus</i>Bacteremia Among Hospitalized Patients
Authors: Elina Eleftheria Pliakos, Panayiotis D. Ziakas, Eleftherios Mylonakis
Journal: JAMA Network Open (2022)

Staphylococcus aureus bacteremia is associated with a significant burden of mortality, morbidity, and health care costs. Infectious disease consultation may be associated with reduced mortality and bacteremia recurrence rates.To evaluate the cost-effectiveness of infectious disease consultation for Staphylococcus aureus bacteremia.In this economic evaluation, a decision-analytic model was constructed comparing infectious disease consult with no consult. The population was adult hospital inpatients with Staphylococcus aureus bacteremia diagnosed with at least 1 positive blood culture. Cost-effectiveness was calculated as deaths averted and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Costs and outcomes were calculated for a time horizon of 6 months. The analysis was performed from a societal perspective and included studies that had been published by January 2022.Patients received or did not receive formal bedside consultation after positive blood cultures for Staphylococcus aureus bacteremia.The main outcomes were incremental difference in effectiveness (survival probabilities), incremental difference in cost (US dollars) and incremental cost-effectiveness ratios (US dollars/deaths averted).This model included 1708 patients who received consultation and 1273 patients who did not. In the base-case analysis, the cost associated with the infectious disease consult strategy was $54 137.4 and the associated probability of survival was 0.77. For the no consult strategy, the cost was $57 051.2, and the probability of survival was 0.72. The incremental difference in cost between strategies was $2913.8, and the incremental difference in effectiveness was 0.05. Overall, consultation was associated with estimated savings of $55 613.4/death averted (incremental cost-effectiveness ratio, -$55613.4/death averted). In the probabilistic analysis, at a willingness-to-pay threshold of $50 000, infectious disease consult was cost-effective compared with no consult in 54% of 10 000 simulations. In cost-effectiveness acceptability curves, the consult strategy was cost-effective in 58% to 73%) of simulations compared with no consult for a willingness-to-pay threshold ranging from $0 to $150 000.These findings suggest that infectious disease consultation may be a cost-effective strategy for management of Staphylococcus aureus bacteremia and that it is associated with health care cost-savings.
Error in Author Name
Journal: JAMA Network Open (2022)

Victor M. Torres-Lopez, MS; Grace E. Rovenolt, BA; Angelo J. Olcese, MS; Gabriella E. Garcia, MD; Sarah M. Chacko; Amber Robinson, MSN; Edward Gaiser, MSN; Julian Acosta, MD; Alison L. Herman, BA; Lindsey R. Kuohn, BA; Megan Leary, BA; Alexandria L. Soto, BS; Qiang Zhang, BS; Safoora Fatima, MD; Guido J. Falcone, MD, ScD, MPH; Seyedmehdi Payabvash, MD; Richa Sharma, MD; Aaron F. Struck, MD; Kevin N. Sheth, MD; M. Brandon Westover, MD, PhD; Jennifer A. Kim, MD, PhD
Primary Care Practitioner Perceptions on the Follow-up of Abnormal Cancer Screening Test Results
Authors: Steven J. Atlas, Anna N. A. Tosteson, Timothy E. Burdick, Adam Wright, Erica S. Breslau, Tin H. Dang, Amy J. Wint, Rebecca E. Smith, Kimberly A. Harris, Li Zhou, Jennifer S. Haas
Journal: JAMA Network Open (2022)

Health care systems focus on delivering routine cancer screening to eligible individuals, yet little is known about the perceptions of primary care practitioners (PCPs) about barriers to timely follow-up of abnormal results.To describe PCP perceptions about factors associated with the follow-up of abnormal breast, cervical, colorectal, and lung cancer screening test results.Survey study of PCPs from 3 primary care practice networks in New England between February and October 2020, prior to participating in a randomized clinical trial to improve follow-up of abnormal cancer screening test results. Participants were physicians and advanced practice clinicians from participating practices.Self-reported process, attitudes, knowledge, and satisfaction about the follow-up of abnormal cancer screening test results.Overall, 275 (56.7%) PCPs completed the survey (range by site, 34.9%-71.9%) with more female PCPs (61.8% [170 of 275]) and general internists (73.1% [201 of 275]); overall, 28,7% (79 of 275) were aged 40 to 49 years. Most PCPs felt responsible for managing abnormal cancer screening test results with the specific cancer type being the best factor (range, 63.6% [175 of 275] for breast to 81.1% [223 of 275] for lung; P < .001). The PCPs reported limited support for following up on overdue abnormal cancer screening test results. Standard processes such as automated reports, reminder letters, or outreach workers were infrequently reported. Major barriers to follow-up of abnormal cancer screening test results across all cancer types included limited electronic health record tools (range, 28.5% [75 of 263]-36.5%[96 of 263]), whereas 50% of PCPs felt that there were major social barriers to receiving care for abnormal cancer screening test results for colorectal cancer. Fewer than half reported being very satisfied with the process of managing abnormal cancer screening test results, with satisfaction being greatest for breast cancer (46.9% [127 of 271]) and lowest for cervical (21.8% [59 of 271]) and lung cancer (22.4% [60 of 268]).In this survey study of PCPs, important deficiencies in systems for managing abnormal cancer screening test results were reported. These findings suggest a need for comprehensive organ-agnostic systems to promote timely follow-up of abnormal cancer screening results using a primary care-focused approach across the range of cancer screening tests.
Association of e-Cigarette Advertising, Parental Influence, and Peer Influence With US Adolescent e-Cigarette Use
Authors: Yu Wang, Zongshuan Duan, Scott R. Weaver, Shannon R. Self-Brown, David L. Ashley, Sherry L. Emery, Jidong Huang
Journal: JAMA Network Open (2022)

Importance Little is known about the roles of advertising and parental and peer influence in e-cigarette use among US adolescents in recent years, hindering efforts to address the increasing rate of youth vaping. Objective To examine how e-cigarette advertising exposure and parental and peer e-cigarette use were associated with e-cigarette use among US adolescents. Design, Setting, and Participants This cohort study used data from waves 4 (December 2016 to January 2018), 4.5 (December 2017 to December 2018), and 5 (December 2018 to November 2019) of the Population Assessment of Tobacco and Health study, an on-going cohort study representative of the noninstitutionalized US population. Sample weights were applied to generate nationally representative estimates. Data were analyzed in January 2022. Exposures Past 30-day e-cigarette advertising exposure, past 30-day parental e-cigarette use, and the number of best friends using e-cigarettes (none, a few, some, most, and all). Main Outcomes and Measures Outcomes were contemporary curiosity about using e-cigarettes and e-cigarette initiation at follow-up. Generalized estimating equations were used to estimate the weighted adjusted associations. Results Wave 4 included 8548 adolescents; wave 4.5, 10 073 adolescents; and wave 5, 11 641 adolescents. Among adolescents in the wave 4 survey, 4425 (51.1%) were boys, 1935 (24.9%) were aged 12 years, 1105 (13.0%) were Black, 2515 (24.4%) were Hispanic, and 3702 (52.3%) were White. More than 60% of adolescents reported past 30-day e-cigarette advertising exposure at each survey. Among adolescents who had never used e-cigarettes, those who reported e-cigarette advertising exposure were more likely to feel curious about using e-cigarettes (adjusted odds ratio [aOR], 1.56 [95% CI, 1.43-1.70]) and were more likely to become ever e-cigarette users (aOR, 1.21 [95% CI, 1.05-1.41]) and current e-cigarette users (aOR, 1.42 [95% CI, 1.16-1.75]) at follow-up. Adolescents who reported having best friends using e-cigarettes were more likely to feel curious about using e-cigarettes (eg, all best friends: aOR, 4.13 [95% CI, 2.35-7.26]) and initiate e-cigarette use at follow-up (eg, among adolescents reporting all best friends use e-cigarettes, risk of ever use: aOR, 4.08 [95% CI, 1.44-11.59]; risk of current use aOR, 5.42 [95% CI, 1.49-19.72]) than adolescents who reported having no best friends using e-cigarettes. Conclusions and Relevance This cohort study of US adolescents found that e-cigarette advertising and peer influence were significantly associated with e-cigarette initiation. Efforts to address youth vaping need to consider peer influence and incorporate measures reducing e-cigarette advertising exposure.
Recommendations for Medical and Mental Health Care in Assisted Living Based on an Expert Delphi Consensus Panel
Authors: Sheryl Zimmerman, Philip D. Sloane, Christopher J. Wretman, Kevin Cao, Johanna Silbersack, Paula Carder, Kali S. Thomas, Josh Allen, Kim Butrum, Tony Chicotel, Pat Giorgio, Mauro Hernandez, Helen Kales, Paul Katz, Juliet Holt Klinger, Margo Kunze, Christopher Laxton, Vicki McNealley, Suzanne Meeks, Kevin O’Neil, Douglas Pace, Barbara Resnick, Lindsay Schwartz, Dallas Seitz, Lori Smetanka, Kimberly Van Haitsma
Journal: JAMA Network Open (2022)

Importance Assisted living (AL) is the largest provider of residential long-term care in the US, and the morbidity of AL residents has been rising. However, AL is not a health care setting, and concern has been growing about residents’ medical and mental health needs. No guidance exists to inform this care. Objective To identify consensus recommendations for medical and mental health care in AL and determine whether they are pragmatic. Evidence Review A Delphi consensus statement study was conducted in 2021; as a separate effort, the extent to which the recommendations are reflected in practice was examined in data obtained from 2016 to 2021 (prepandemic). In the separate effort, data were from a 7-state study (Arkansas, Louisiana, New Jersey, New York, Oklahoma, Pennsylvania, Texas). The 19 Delphi panelists constituted nationally recognized experts in medical, nursing, and mental health needs of and care for older adults; dementia care; and AL and long-term care management, advocacy, regulation, and education. One invitee was unavailable and nominated an alternate. The primary outcome was identification of recommended practices based on consensus ratings of importance. Panelists rated 183 items regarding importance to care quality and feasibility. Findings Consensus identified 43 recommendations in the areas of staff and staff training, nursing and related services, resident assessment and care planning, policies and practices, and medical and mental health clinicians and care. To determine the pragmatism of the recommendations, their prevalence was examined in the 7-state study and found that most were in practice. The items reflected the tenets of AL, the role of AL in providing dementia care, the need for pragmatism due to the diversity of AL, and workforce needs. Conclusions and Relevance In this consensus statement, 43 recommendations important to medical and mental health care in AL were delineated that are highly pragmatic as a guide for practice and policy.